title: Sarcosine and other metabolites along the choline oxidation pathway in relation to prostate cancer--a large nested case-control study within the JANUS cohort in Norway.
abstract: Methyl group donors and intermediates of one-carbon metabolism affect DNA synthesis and DNA methylation, and may thereby affect prostate carcinogenesis. Choline, the precursor of betaine, and the one-carbon metabolite sarcosine have been associated with increased prostate cancer risk. Within JANUS, a prospective cohort in Norway (n = 317,000) with baseline serum samples, we conducted a nested case-control study among 3,000 prostate cancer cases and 3,000 controls. Using conditional logistic regression, odds ratios (ORs) and 95% confidence intervals (CIs) for prostate cancer risk were estimated according to quintiles of circulating betaine, dimethylglycine (DMG), sarcosine, glycine and serine. High sarcosine and glycine concentrations were associated with reduced prostate cancer risk of borderline significance (sarcosine: highest vs. lowest quintile OR = 0.86, CI = 0.72-1.01, p(trend) = 0.03; glycine: OR = 0.83, CI = 0.70-1.00, p(trend) = 0.07). Serum betaine, DMG and serine were not associated with prostate cancer risk. However, individuals with a high glycine/serine ratio were at decreased prostate cancer risk (OR = 0.74, CI = 0.69-0.85, p(trend) < 0.001). This population-based study suggested that men with high serum sarcosine or glycine concentrations have modestly reduced prostate cancer risk. Ratios of metabolites reflecting one-carbon balance may be associated with prostate cancer risk, as demonstrated for the glycine/serine ratio, and should be explored in future studies.
authors.affiliation: Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
authors.forename: Stefan
authors.initials: S
authors.lastname: de Vogel
authors.forename: Arve
authors.initials: A
authors.lastname: Ulvik
authors.forename: Klaus
authors.initials: K
authors.lastname: Meyer
authors.forename: Per Magne
authors.initials: PM
authors.lastname: Ueland
authors.forename: Ottar
authors.initials: O
authors.lastname: Nygård
authors.forename: Stein Emil
authors.initials: SE
authors.lastname: Vollset
authors.forename: Grethe S
authors.initials: GS
authors.lastname: Tell
authors.forename: Jesse F
authors.initials: JF
authors.lastname: Gregory
authors.forename: Steinar
authors.initials: S
authors.lastname: Tretli
authors.forename: Tone
authors.initials: T
authors.lastname: Bjørge
mesh_terms: D001622:Betaine / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D002794:Choline / Q000378:metabolism*; D002853:Chromatography, Liquid; D015331:Cohort Studies; D005998:Glycine / Q000097:blood*; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009664:Norway; D010084:Oxidation-Reduction; D011471:Prostatic Neoplasms / Q000378:metabolism*; D012521:Sarcosine / Q000031:analogs & derivatives / Q000097:blood*; D012694:Serine / Q000097:blood
chemical_list: D014408:Biomarkers, Tumor; D001622:Betaine; D012694:Serine; C025138:dimethylglycine; D002794:Choline; D005998:Glycine; D012521:Sarcosine
keywords: case-control study; choline oxidation pathway; population-based; prostate cancer risk; sarcosine